Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
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Article Citation - WoS: 139Granulocytic Sarcoma: a Systematic Review(e-Century Publishing Corporation, 2013) Yılmaz, Asu Fergün; Saydam, Güray; Şahin, Fahri; Baran, YusufGranulocytic sarcoma also called myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukemia and myelodysplastic syndromes. In some rare circumstances, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the granulocytic sarcoma is described as nonleukemic, primary or isolated. It is observed at any part of the body but the most common locations are soft tissues, bone, peritoneum and lymph nodes. Presenting signs or symptoms are mainly due to mass effect of the tumor and dysfunction of the organ, or the tissue that is affected. The diagnosis is performed by biopsy of the tumor. The tumor consists of immature granulocytic cells, which could be documented by H&E, immunohistochemistry, and flow cytometric methods. Fluorescence in-situ hybridization and molecular analysis are also performed. The optimal time and type of treatment is not clear. Surgery could be an option especially for tumors, which cause organ dysfunction and/or obstruction. Systemic treatment should be considered in all patients because without systemic treatment, relapses and progression to acute myeloid leukemia is the ultimate fate of the disease in many cases. Cytarabine-containing remission-induction chemotherapies have been the most applied therapeutic strategies, but it is not clear whether the consolidation therapies are required or not, and what kind of regimens are appropriate. The role of hematopoietic stem cell transplantation (HSC) as a consolidation regimen is not clear, but, after the relapse of the disease with or without bone marrow involvement, HSC transplantation should be considered in suitable patients after the reinduction performed by AML chemotherapies. There is only limited data about the role of radiotherapy in these patients. It could be used in patients with relapsed disease, organ dysfunction which should be quickly relieved and inadequate response to chemotherapy. The effect of radiotherapy on overall survival is not known. New prospective studies and clinical trials are needed to generate guidelines for the treatment of primary granulocytic sarcomas.Article Citation - WoS: 15Citation - Scopus: 13Cascade Therapy With Doxorubicin and Survivin-Targeted Tailored Nanoparticles: an Effective Alternative for Sensitization of Cancer Cells To Chemotherapy(Elsevier Ltd., 2019) Dağlıoğlu, Cenk; Kacı, Fatma NecmiyeChemotherapy frequently involves combination treatment protocols to maximize tumor cell killing. Unfortunately these intensive chemotherapeutic regimes, often show disappointing results due to the development of drug resistance and higher nonspecific toxicity on normal tissues. In cancer treatment, it is critically important to minimize toxicity while preserving efficacy. We have previously addressed this issue and proposed a nanoparticle-based combination therapy involving both a molecularly targeted therapy and chemotherapeutic agent for neutralizing antiapoptotic survivin (BIRC5) to potentiate the efficacy of doxorubicin (DOX). Although the particles exhibited strong anticancer effect on the lung carcinoma A549 and the cervical carcinoma HeLa cells, there were lower-level therapeutic outcomes on the colon carcinoma HCT-116, the leukemia Jurkat and the pancreatic carcinoma MIA PaCa-2 cells. Since targeted therapies are one of the key approaches for overcoming drug resistance, tailoring the treatment of cancer cells with distinct characteristics is necessary to improve the therapeutic outcome of cancer therapy and to minimize potential pharmacokinetic interactions of drugs. In the light of this issue, this study examined whether a cascade therapy with low-dose DOX and survivin-targeted tailored nanoparticles is more effective at sensitizing HCT-116, Jurkat and MIA PaCa-2 cancer cells to DOX-chemotherapy than simultaneous combination therapy. The results demonstrated that the sequential therapy with the protocol comprising addition of the nanoparticles after incubation of cells with DOX clearly advanced the therapeutic outcome of related cancer cells, whereas the reverse protocol resulted in a reduction or delay in apoptosis, emphasizing the critical importance of formulating synergistic drug combinations in cancer therapy.Article Citation - WoS: 6Citation - Scopus: 6Bioactive Sphingolipids in Response To Chemotherapy: a Scope on Leukemias(Bentham Science Publishers B.V., 2011) Ekiz, Hüseyin Atakan; Baran, YusufSphingolipids are major constituents of the cells with emerging roles in the regulation of cellular processes. Deregulation of sphingolipid metabolism is reflected as various pathophysiological conditions including metabolic disorders and several forms of cancer. Ceramides, ceramide-1-phosphate (C1P), glucosyl ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P) are among the bioactive sphingolipid species that have important roles in the regulation of cell death, survival and chemotherapeutic resistance. Some of those species are known to accumulate in the cells upon chemotherapy while some others are known to exhibit an opposite pattern. Even though the length of fatty acid chain has a deterministic effect, in general, upregulation of ceramides and sphingosine is known to induce apoptosis. However, S1P, C1P and GluCer are proliferative for cells and they are involved in the development of chemoresistance. Therefore, sphingolipid metabolism appears as a good target for the development of novel therapeutics or supportive interventions to increase the effectiveness of the chemotherapeutic drugs currently in hand. Some approaches involve manipulation of the synthesis pathways yielding the increased production of apoptotic sphingolipids while the proliferative ones are suppressed. Some others are trying to take advantage of cytotoxic sphingolipids like short chain ceramide analogs by directly delivering them to the malignant cells as a distinct chemotherapeutic intervention. Numerous studies in the literature show the feasibility of those approaches especially in acute and chronic leukemias. This review compiles the current knowledge about sphingolipids and their roles in chemotherapeutic response with the particular attention to leukemias. © 2011 Bentham Science Publishers Ltd.Article Citation - WoS: 4Citation - Scopus: 7The Importance of Protein Profiling in the Diagnosis and Treatment of Hematologic Malignancies(Galenos Yayıncılık, 2011) Şanlı Mohamed, Gülşah; Turan, Taylan; Ekiz, Hüseyin Atakan; Baran, YusufProteins are important targets in cancer research because malignancy is associated with defects in cell protein machinery. Protein profiling is an emerging independent subspecialty of proteomics that is rapidly expanding and providing unprecedented insight into biological events. Quantitative assessment of protein levels in hematologic malignancies seeks a comprehensive understanding of leukemiaassociated protein patterns for use in aiding diagnosis, follow-up treatment, and the prediction of clinical outcomes. Many recently developed high-throughput proteomic methods can be applied to protein profiling. Herein the importance of protein profiling, its exploitation in leukemia research, and its clinical usefulness in the treatment and diagnosis of various cancer types, and techniques for determining changes in protein profiling are reviewed.Article Citation - WoS: 31Citation - Scopus: 36Quercetin-Induced Apoptosis Involves Increased Htert Enzyme Activity of Leukemic Cells(Taylor and Francis Ltd., 2011) Avcı, Çığır Biray; Yılmaz, Sunde; Doğan, Zeynep Özlem; Saydam, Güray; Dodurga, Yavuz; Ekiz, Hüseyin Atakan; Kartal, Melis; Şahin, Fahri; Baran, Yusuf; Gündüz, CumhurWe aimed to examine the growth suppressive effects of quercetin on acute promyelocytic and lymphoblastic leukemia and chronic myeloid leukemia, and to find out whether the growth suppression is related to the blocking of telomerase enzyme activity. Cytotoxic effects of quercetin were shown by trypan blue analyses. Apoptotic effects of quercetin were examined by acridine orange and ethidium bromide staining by fluorescence microscopy. The effects of quercetin on telomerase enzyme activity were shown by hTERT Quantification Kit. Our results demonstrated that quercetin has antiproliferative and apoptotic effects on T-cell acute lymphoblastic leukemia (ALL), acute promyelocytic leukemia, and chronic myeloid leukemia (CML) cells. We also showed for the first time by this study that quercetin suppresses the activity of telomerase in ALL and CML cells. The results of this study show the importance of quercetin for its therapeutic potential in treatment of leukemias.Article Citation - WoS: 23Citation - Scopus: 25Role of Autophagy in the Progression and Suppression of Leukemias(Elsevier Ltd., 2012) Ekiz, Hüseyin Atakan; Can, Geylani; Baran, YusufAutophagy is a physiological process in which cellular components are degraded by the lysosomal machinery. Thereby, organelles are recycled and monomers are produced in order to maintain energy production. Current studies indicate autophagy might suppress or augment survival of cancer cells. Therefore, by elucidating the role of autophagy in cancer pathogenesis, novel therapeutic intervention points may be revealed. Leukemia therapy has advanced in recent years; but a definitive cure is still lacking. Since autophagy often is deregulated in this particular type of cancer, it is clear that future findings will have clinical implications. This review will discuss the current knowledge of autophagy in blood cancers. © 2011 Elsevier Ireland Ltd.Article Citation - WoS: 32Citation - Scopus: 34Therapeutic Applications of Bioactive Sphingolipids in Hematological Malignancies(John Wiley and Sons Inc., 2010) Ekiz, Hüseyin Atakan; Baran, YusufSphingolipids are sphingosine-based lipid molecules that have important functions in cellular signal transduction and in a variety of cellular processes including proliferation, differentiation, programmed cell death (apoptosis) and responses to stressful conditions. Ceramides, dihydroceramide, sphingosine and sphingosine-1-phosphate are examples of those bioactive sphingolipids. They have a major impact on determination of the cell fate by contributing to the cell survival or cell death through apoptosis. Despite the number of carbon atoms in the fatty acid chain changes the physiological role; ceramides generally exert suppressive roles on the cell proliferation. There have been several enzymes identified in this pathway that are responsible for the conversion of ceramide into other sphingolipid derivatives. Those derivatives also have differential roles on those cellular processes. Sphingosine-1-phosphate is an example of such sphingolipid derivatives which has antiapoptotic effects. As they have significant impacts particularly on the cell death and survival, bioactive sphingolipids have a great potential to be targets in cancer therapy. Increasing number of studies indicates that sphingolipid derivatives are important in the progression of hematological malignancies, and they are also involved in the resistance to current chemotherapeutic options. This review compiles the current knowledge in this area for enlightening the therapeutic potentials of bioactive sphingolipids in various leukemias. © 2010 UICC.